CRISPR-Cas Systems in , an Important Pathobiont in the Human Gut Microbiome.

While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus make up ~25% of the total gut microbiome. comprises only 2% of the total in the gut, yet causes of >70% of infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT) of virulence genes and differential transcription of endogenous genes are clearly involved. The CRISPR-Cas system is a multi-functional system described in prokaryotes that may be involved in control both of HGT and of gene regulation. Clustered regularly interspaced short palindromic repeats (CRISPR) elements in all strains of ( = 109) with publically available genomes were identified. Three different CRISPR-Cas types, corresponding most closely to Type IB, Type IIIB, and Type IIC, were identified. Thirty-five strains had two CRISPR-Cas types, and three strains included all three CRISPR-Cas types in their respective genomes. The gene in the Type IIIB system encoded a reverse-transcriptase/Cas1 fusion protein rarely found in prokaryotes. We identified a short CRISPR (3 DR) with no associated genes present in most of the isolates; these CRISPRs were found immediately upstream of a operon and we speculate that this element may be involved in regulation of this operon related to formation of persister cells during antimicrobial exposure. Also, blood isolates of did not have Type IIC CRISPR-Cas systems and had atypical Type IIIB CRISPR-Cas systems that were lacking adjacent genes. This is the first systematic report of CRISPR-Cas systems in a wide range of strains from a variety of sources. There are four apparent CRISPR-Cas systems in -three systems have adjacent genes. Understanding CRISPR/Cas function in will elucidate their role in gene expression, DNA repair and ability to survive exposure to antibiotics. Also, based on their unique CRISPR-Cas arrays, their phylogenetic clustering and their virulence potential, we are proposing that blood isolates of be viewed a separate subgroup.